Practice Rational Testing

Investigating an incidental finding of a paraprotein

BMJ 2012; 344 doi: (Published 04 May 2012) Cite this as: BMJ 2012;344:e3033

Re: Investigating an incidental finding of a paraprotein

Para protein is an incomplete monoclonal immunoglobulin like Cryoglobulin, myeloma protein, macroglobulin. They are various plasma cell disorders. Cryoglobulin (especially IgG and IgM) is grouped with gamma globulin and characterised by precipitating, gelling or crystallising when serum or solutions are cooled. They have a lower molecular weight than bence jones protein. They are associated with multiple myeloma, hepatitis C and hepatitis B induced vasculitis, systemic lupus erythematosus and rheumatoid arthritis. Classified by Brout [1] ,the type II and III have rheumatoid factor (RF) and bind to polyclonal immunoglobulin. They are denoted as mixed Cryoglobinuria, in which when the temperature is raised, the precipitated Cryoglobulin will dissolve back into the serum [2]. Cryoglobulin (which is a cold insoluble immune complex) may contribute to medium size arteritis and gangrene. Other common constitutional symptoms are fatigue, low grade fever, fibromyalgia[3], articular involvement, vascular involvement (purpura, skin ulcer, necrotic skin lesions such as necrotising vasculitis), Raynaud’s phenomenon, hyper viscosity syndrome and neurological involvement such as peripheral neuropathy. A subset of patients develop low grade lymphoma. Necrotising vasculitis, with fibrinoid necrosis of the inflammation of the entire vessel wall and perivascular space, may also occur. Neurological involvement is variable leading to occasional sensorimotor neuropathy arising from Cryoglobulin deposition in the vasa vasorum. This can cause mononeuritis and foot drop.

1. Brouet JC,Clauvul JP,Danon F,Klein M ,Seligmann M(1974).Biologic and clinical significance og Cryoglobulin .A report of 86 cases.Am J Med . 57 (5):775 -88.
2. Tederchi A, Barrate C, Minola E, Morra E (2007).Cryoglobulinemia.Blood Rev. 21(4):183 -200.
3. Wolfe F,Smythe HA ,Yunus MB et al.The American College of Rheumatology 1990 Criteria for the classification of fibromyalgia.Report of the multicentre criteria committee .Arthritis Rheumatism 1990 ; 33:160 -172.
4. Authies FJ,Pawlotsky JM,Viard JP,et al .High incidence of hepatitis C virus infection inpatient with Cryoglobulinemic neuropathy .Ann Neurol. 1993 ;34:749 -750.

Competing interests: No competing interests

03 January 2013
Kaushik Sanyal
Department of Rheumatology
East Surrey Hospital
Redhill , Surrey